Pre- and Post-treatment Lung Microbiota, Metabolome and Immune Signatures at the Site of Disease in Patients With Active Pulmonary Tuberculosis
The diverse microbial communities in different parts of the human body (microbiome) are important for health but understudied in pulmonary tuberculosis (TB), which is the single biggest infectious cause of death in the world. The investigators will study the site-of-disease microbiome (in the lung bronchoalveolar space) in TB cases to investigate how, before TB treatment, metabolic compounds made by microbes affect host biomarkers important for TB control. The investigators will ask this question again at the end-of-treatment and one year later. Specifically, the investigators will sample the lung at the active TB hotspot identified by imaging and compare this to a non-involved lung segment usually in the opposite lung. The investigators will compare the lung microbiome to other sites in the body (i.e. oral cavity, nasopharynx, supraglottis, and gut). A small amount of blood (\ 15 ml) will be collected to assess peripheral immunological correlates of the host microbiome. Protected specimen brushings of the lung will be used to explore transcriptomic signatures and how these relate to the lung microbiome. The investigators will also apply these questions to the same number of controls (healthy patients and patients with an alternative diagnoses). This will lay the foundation for clinical trials to evaluate if specific bacteria have diagnostic (e.g., PCR) or therapeutic potential (e.g., antibiotics, prebiotics, probiotics, vaccines) where targeting the microbiome could improve clinical outcomes.
• 18-60 years old.
• Agree to undergo CXR and/or CT scan.
• Has unilateral TB disease defined as one lung with extensive evidence of TB disease (non-applicable to healthy controls; sick controls will require an alternative diagnosis).
• No evidence of prior TB treatment and/or CXR/CT does not have obvious evidence of prior TB.
• Willing to undergo a research bronchoscopy at baseline, 6 months and 18 months and likely to remain in the area for the study period.
• If HIV-positive, must be stable on antiretroviral therapy (ART) for ≥1 year.
• Able and willing to return for follow-up visits, with no plans to move in the near future.
• Willing to comply with study requirements i.e. provision of contact details and written, informed consent prior to enrolment.